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Fibromyalgia (FM) is a central sensitization syndrome that is strongly associated with the cerebral cortex. This study used bidirectional two-sample Mendelian randomization (MR) analysis to investigate the bidirectional causality between FM and the cortical surface area and cortical thickness of 34 brain regions. Inverse variance weighted (IVW) was used as the primary method for this study, and sensitivity analyses further supported the results. The forward MR analysis revealed that genetically determined thinner cortical thickness in the parstriangularis (OR = 0.0567 mm, PIVW = 0.0463), caudal middle frontal (OR = 0.0346 mm, PIVW = 0.0433), and rostral middle frontal (OR = 0.0285 mm, PIVW = 0.0463) was associated with FM. Additionally, a reduced genetically determined cortical surface area in the pericalcarine (OR = 0.9988 mm2, PIVW = 0.0085) was associated with an increased risk of FM. Conversely, reverse MR indicated that FM was associated with cortical thickness in the caudal middle frontal region (ß = -0.0035 mm, PIVW = 0.0265), fusiform region (ß = 0.0024 mm, SE = 0.0012, PIVW = 0.0440), the cortical surface area in the supramarginal (ß = -9.3938 mm2, PIVW = 0.0132), and postcentral regions (ß = -6.3137 mm2, PIVW = 0.0360). Reduced cortical thickness in the caudal middle frontal gyrus is shown to have a significant relationship with FM prevalence in a bidirectional causal analysis.
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Corteza Cerebral , Fibromialgia , Humanos , Fibromialgia/genética , Fibromialgia/diagnóstico por imagen , Fibromialgia/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Análisis de la Aleatorización Mendeliana , Imagen por Resonancia Magnética , Femenino , Predisposición Genética a la Enfermedad/genética , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association. METHODS: We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran's Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings. RESULTS: No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892-0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888-0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy. CONCLUSION: While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.
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OBJECTIVE: Intraspinal cysts are uncommon, and the success rate of complete resection is still low for spinal neurenteric cysts (NCs). The aim of this study was to evaluate the efficacies of an anterior microscopic surgical approach in the treatment of ventral and ventrolateral subaxial cervical NCs (SCNCs). METHODS: Between 2019 and 2022, 9 patients with NCs of the subaxial spine underwent an anterior microsurgical approach. Their clinical presentations, radiological features, operative findings, and follow-up data were retrospectively reviewed and analyzed. RESULTS: All spinal cysts were intradural and extramedullary in origin. Five patients were first-time cases while 4 patients with recurrence underwent revision surgery. The most common clinical manifestation was pain (77.78%). One patient was found to have a concomitant disorder of Klippel-Feil syndrome. Microscopically confirmed gross-total resection was achieved in 8 patients (88.89%) based on clinical comparisons between pre- and postoperative MRI and intraoperative video. One patient had symptom recurrence 1 year after subtotal resection, while there was no evidence of recurrence during follow-up for the other patients. Dense adhesions within the spinal cord were observed in 8 patients (88.89%) intraoperatively. Most importantly, the surgical outcome was significantly improved in all patients, and the mean (± SE) Japanese Orthopaedic Association score increased from 11.33 ± 0.91 preoperatively to 16.22 ± 0.32 postoperatively (p = 0.008). CONCLUSIONS: An anterior surgical approach was proven to be both safe and effective in treating the ventral or ventrolateral SCNCs. The authors believe that an anterior microsurgical approach should be considered as a useful approach especially in patients with ventral recurrent SCNCs. Its clinical efficacy compared with a posterior approach in ventral spinal cyst may be better as most of the neurenteric cysts are ventrally or ventrolaterally located.
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OBJECTIVE: The optimal choice for fusion strategy in Anterior Cervical Discectomy and Fusion (ACDF) remains an unresolved issue. This study aims to perform a network meta-analysis and systematic review of fusion rate and complication rate of various fusion strategies used in ACDF. METHODS: This study followed Prisma guidelines, and we searched PubMed, Embase, Cochrane Library, and Web of Science from inception to November 11, 2022, for Randomized Controlled trials comparing the efficacy and safety of fusion modalities in ACDF. The primary outcome was the fusion rate and complication rate. The PROSPERO number is CRD42022374440. RESULTS: This meta-analysis identified 26 Randomized Controlled trial studies with 1789 patients across 15 fusion methods. The cage with autograft + plating showed the highest fusion rate, surpassing other methods like iliac crest bone graft (ICBG) and artificial bone graft (AFG). The stand-alone cage with autograft (SATG) had the second highest fusion rate. Regarding complication rate, the cage with AFG (CAFG) had the highest rate, more than other methods. The ICBG had a higher complication rate compared to ICBG + P, AFG, stand-alone cage with artificial bone graft, SATG, and CALG. The SATG performed well in both fusion and complication rate. CONCLUSIONS: In this study, we conducted the first network meta-analysis to compare the efficacy and safety of various fusion methods in ACDF. Our findings suggest that SATG, with superior performance in fusion rate and complication rate, may be the optimal choice for ACDF. However, the results should be interpreted cautiously until additional research provides further evidence.
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Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302-1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237-1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395-1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019-1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007-1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02-1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%-12.10%) for any stroke, 11.77% (95% CI: 10.58%-12.97%) for IS, 10.62% (95% CI: 8.04%-13.20%) for LAS, and 7.57% (95% CI: 6.79%-8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.
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Trastorno del Espectro Autista , Enfermedades Cardiovasculares , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular , Humanos , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/epidemiología , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/epidemiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Predisposición Genética a la EnfermedadRESUMEN
BACKGROUND: Previous studies on the relationship between systemic lupus erythematosus (SLE) and autoimmune liver diseases (AILDs) are inconclusive. Therefore, we employed Mendelian randomization (MR) to explore the causal associations between SLE and AILDs. METHODS: A two-sample MR analysis was performed using summary-level statistics sourced from genome-wide association study (GWAS) datasets. Inverse-variance weighting (IVW), MRâEgger, and weighted median (WM) were further supported by several sensitivity analyses. RESULTS: We detected causal genetic associations between SLE and primary biliary cholangitis (PBC) (odds ratio (OR) = 1.31, 95% CI = 1.15-1.51, P < 0.01; adjusted OR = 1.63, 95% CI = 1.39-1.90, P < 0.01) and between SLE and primary sclerosing cholangitis (PSC) (OR = 1.09, 95% CI = 1.01-1.08, P = 0.03; adjusted OR = 1.10, 95% CI = 1.00-1.21, P = 0.04). No causal association was found between SLE and autoimmune hepatitis. CONCLUSIONS: We are the first to use MR analysis to explore the causal relationships between SLE and various AILDs, revealing an increased risk of PBC and PSC in individuals with SLE.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Lupus Eritematoso Sistémico , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/epidemiología , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/epidemiología , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/epidemiología , Cirrosis Hepática Biliar/etiología , Colangitis Esclerosante/genética , Colangitis Esclerosante/epidemiología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/etiología , Oportunidad Relativa , Factores de Riesgo , Hepatopatías/genética , Hepatopatías/epidemiología , Hepatopatías/etiologíaRESUMEN
BACKGROUND: Growing evidence suggested that particulate matter (PM) exhibit an increased risk of autism spectrum disorder (ASD). However, the causal association between PM and ASD risk remains unclear. METHODS: We performed two-sample Mendelian randomization (MR) analyses, using instrumental variables (IVs) sourced from the largest genome-wide association studies (GWAS) databases. We employed three MR methods: inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, with IVW method serving as our primary MR method. Sensitivity analyses were performed to ensure the stability of these findings. RESULTS: The MR results suggested that PM2.5 increased the genetic risk of ASD (ß = 2.41, OR = 11.13, 95% CI: 2.54-48.76, P < 0.01), and similar result was found for PM2.5 absorbance (ß = 1.54, OR = 4.67, 95% CI: 1.21-18.01, P = 0.03). However, no such association was found in PM10 (ß = 0.27, OR = 1.30, 95% CI: 0.72-2.36, P = 0.38). After adjusting for the false discovery rate (FDR) correction, our MR results remain consistent. Sensitivity analyses did not find significant heterogeneity or horizontal pleiotropy. CONCLUSIONS: Our findings indicate that PM2.5 is a potential risk factor for ASD. Effective strategies to mitigate air pollutants might lead to a reduced incidence of ASD.
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Trastorno del Espectro Autista , Material Particulado , Humanos , Material Particulado/efectos adversos , Trastorno del Espectro Autista/genética , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Bases de Datos FactualesRESUMEN
PURPOSE: The previous studies have suggested that serum homocysteine (Hcy) and vitamin B levels are potentially related to autism spectrum disorder (ASD). However, the causality between their concentrations and ASD risk remains unclear. To elucidate this genetic association, we used a Mendelian randomization (MR) design. METHODS: For this MR analysis, 47 single-nucleotide polymorphisms (SNPs)-13 related to Hcy, 13 to folate, 14 to vitamin B6, and 7 to vitamin B12-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). Our study used three approaches to calculate the MR estimates, including inverse-variance weighted (IVW) method, MR-Egger method, and weighted median (WM) method. Among these, the IVW method served as our primary MR method. False discovery rate (FDR) was implemented to correct for multiple comparisons. We also performed a series of sensitivity analyses, including Cochran's Q test, MR-Egger's intercept, MR-PRESSO, leave-one-out analysis, and the funnel plot. RESULTS: Univariable Mendelian randomization (UVMR) analysis revealed a statistical association between serum vitamin B12 levels and ASD risk (OR = 1.68, 95% CI 1.12-2.52, P = 0.01) using the IVW method. However, neither the WM method (OR = 1.57, 95% CI 0.93-2.66, P = 0.09) nor the MR-Egger method (OR = 2.33, 95% CI 0.48-11.19, P = 0.34) was significantly association with higher levels of serum vitamin B12 and ASD risk. Additionally, we found no evidence of causal relationships between serum levels of vitamin B6, folate, Hcy, and ASD risk. After correcting for the FDR, the causality between serum vitamin B12 levels and ASD risk remained significant (q value = 0.0270). Multivariate Mendelian randomization (MVMR) analysis indicated an independent association between elevated serum vitamin B12 levels and the risk of ASD (OR = 1.74, 95% CI 1.03-2.95, P = 0.03) using the IVW method, but this finding was inconsistent when using the WM method (OR = 1.73, 95% CI 0.89-3.36, P = 0.11) and MR-Egger method (OR = 1.60, 95% CI 0.95-2.71, P = 0.08). Furthermore, no causal associations were observed for serum levels of vitamin B6 and folate in MVMR analysis. Sensitivity analyses confirmed that these results were reliable. CONCLUSION: Our study indicated that elevated serum vitamin B12 levels might increase the risk of ASD. The potential implications of our results for ASD risk warrant validation in randomized clinical trials.
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Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Trastorno del Espectro Autista/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Vitaminas , Ácido Fólico , Vitamina B 6 , Vitamina B 12 , HomocisteínaRESUMEN
Purpose: Neuromyelitis optica spectrum disorder (NMOSD) is a rare recurrent autoimmune disease of the central nervous system. However, to date, the peripheral blood profile of the T helper cell subsets in NMOSD remains controversial and poorly understood. This study aimed to compare the levels of helper T cell subsets in the peripheral blood from patients with NMOSD in different phases of the disease and studied their correlation with the clinical severity of the disease. Patients and methods: We used flow cytometry with cellular membrane surface staining to measure the levels of helper T cell subsets in 50 patients with NMOSD during the attack (n = 25) and remission (n = 25) phases and in 21 healthy controls. Results: Patients with NMOSD had higher levels of Th1 and Th17 cells in the attack phase compared to parallel populations in the remission phase and healthy controls. Th1/Th2 and Th17/Treg ratios were positively correlated with the severity of the disease in the attack phase of NMOSD. In contrast, Treg cell levels were negatively correlated with the severity of the disease in the attack phase in patients with NMOSD. Conclusion: The peripheral blood immune profile in NMOSD towards a Th1/Th17 cell-mediated pro-inflammatory immune response, which is associated with disease activity and severity of neuromyelitis optica spectrum disorder.
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BACKGROUND: Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed. METHODS: In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study. RESULTS: At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403-0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157-3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128-3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072-1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071-1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran's Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC. CONCLUSIONS: Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.
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Microbioma Gastrointestinal , Neoplasias Pancreáticas , Humanos , Microbioma Gastrointestinal/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Neoplasias Pancreáticas/genética , Neoplasias PancreáticasRESUMEN
BACKGROUND: More early-stage non-small cell lung cancer (NSCLC) are diagnosed in time and treated surgically, but systematic lymph node dissection can not bring enough survival benefits for them, and even increase the probability of postoperative complications. This study aims to analyze the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes for NSCLC with diameter ≤2 cm, so as to provide reference for surgery. METHODS: We collected 1051 patients with pulmonary nodule diameter ≤2 cm who were treated by pulmonary lobectomy with lymph node sampling/dissection in Department of Thoracic Surgery of the First Affiliated Hospital with Nanjing Medical University from December 2009 to December 2019. SPSS 26.0 statistical software was used for statistical analysis, to explore the risk factors and evaluate mediastinal lymph node metastasis sites in different lung lobes. RESULTS: 95 of 1051 (9.04%) patients presented lymph node metastasis. Male, pathological non-adenocarcinoma, 1 cmAsunto(s)
Adenocarcinoma
, Carcinoma de Pulmón de Células no Pequeñas
, Neoplasias Pulmonares
, Carcinoma Pulmonar de Células Pequeñas
, Humanos
, Masculino
, Carcinoma de Pulmón de Células no Pequeñas/cirugía
, Metástasis Linfática
, Neoplasias Pulmonares/cirugía
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Background: Numerous observational studies have suggested that atrial fibrillation (AF) was associated with an increased risk of vascular dementia (VaD). However, the causal genetic relationships between AF and VaD remains unclear. To evaluate the effect of AF on VaD, we performed the Mendelian randomization (MR) analysis to investigate the causal genetic relationships between AF and VaD. Methods: The bidirectional MR analysis was conducted to explore the causal relationships between exposure and disease. We applied a series of quality assessments to select significantly and independently single nucleotide polymorphisms (SNPs) from publicly available large-scale genome-wide association studies (GWAS) databases. Three methods [Inverse variance weighted method (IVW), MR-Egger method, and weighted median (WM)method] were used to derive MR estimates. In order to ensure reliable MR results, sensitivity analyses were performed to evaluate the horizontal pleiotropy and heterogeneity. Results: Our MR analyses revealed no significant genetic relationships between AF and the risk of VaD (IVW: OR = 1.10, 95%CI = 0.95-1.28, P = 0.20). In the reverse direction analysis, there was no evidence to support a significant genetic relationship of VaD with AF risk (IVW: OR = 1.00, 95% CI = 0.99-1.01, P = 0.52). Consistent results were obtained using different MR methods. Sensitivity analyses suggested no significant horizontal pleiotropy and heterogeneity in the study. Conclusion: This MR analysis did not provide evidence to support the causal genetic relationships between AF on VaD risk and the causal effect of VaD on AF risk.
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OBJECTIVES: Vitamin D has been linked to diabetic neuropathy (DN) in previous epidemiological observational studies, however, their findings are inconsistent. The causal relationship between vitamin D and DN remains unknown. In this study we aim to investigate the causal association of serum 25-hydroxyvitamin D (25OHD) and DN. METHODS: Based on summary statistics from publicly available genome-wide association studies (GWAS) database, we detected the genetic correlation between serum 25OHD levels and DN by a two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary analysis, weighted median and MR-Egger were applied as complementary methods for MR estimates. In addition, we took sensitivity analyses including Cochran's Q test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and leave-one-out analysis to ensure that we obtained stable and reliable results. RESULTS: Our MR study showed no significant genetic association between serum 25OHD levels and DN (OR = 1.13, 95% CI = 0.81-1.57, P = 0.46). Furthermore, in the reverse direction analysis, we did not find a significant causal effect of DN and serum 25OHD levels (OR = 0.99, 95% CI = 0.98-1.00, P = 0.09). Results of MR-Egger, Weighted Median were consistent with those of the IVW method. The sensitivity analysis suggesting that no significant heterogeneity and genetic pleiotropy was observed. CONCLUSIONS: Our results provided no evidence to support the causal association of serum 25OHD levels with DN.
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Diabetes Mellitus , Neuropatías Diabéticas , Humanos , Análisis de la Aleatorización Mendeliana , Neuropatías Diabéticas/genética , Estudio de Asociación del Genoma Completo , Vitamina D , Vitaminas , Polimorfismo de Nucleótido SimpleRESUMEN
Humic substances are widely present in aquatic environments. Due to the high affinity of humic substances for metals, the interactions have been particularly studied. To assess the effect of humic acid (HA) on submerged macrophytes and biofilms exposed to heavy metal stress, Vallisneria natans was exposed to solutions containing different concentrations of HA (0.5-2.0 mg·L-1), Pb2+ (1 mg·L-1) and Cd2+ (1 mg·L-1). Results suggested that HA positively affected the plant growth and alleviated toxicity by complexing with metals. HA increased the accumulation of metals in plant tissues and effectively induced antioxidant responses and protein synthesis. It was also noted that the exposure of HA and metals promoted the abundance and altered the structure of microbial communities in biofilms. Moreover, the positive effects of HA were considered to be related to the expression of related genes resulting from altered DNA methylation levels, which were mainly reflected in the altered type of demethylation. These results demonstrate that HA has a protective effect against heavy metal stress in Vallisneria natans by inducing effective defense mechanisms, altering biofilms and DNA methylation patterns in aquatic ecosystems.
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Hydrocharitaceae , Metales Pesados , Microbiota , Sustancias Húmicas/análisis , Cadmio/metabolismo , Plomo/toxicidad , Plomo/metabolismo , Metales Pesados/metabolismo , Hydrocharitaceae/metabolismoRESUMEN
OBJECTIVE: Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease affecting women of childbearing age. We aimed to conduct a meta-analysis of published observational studies to systematically evaluate the association between RA and adverse pregnancy outcomes. METHODS: Medline (PubMed), EMBASE, and Web of Science were searched for keywords from the date of inception to December 28, 2021, to identify relevant studies reporting adverse maternal and/or fetal outcomes in RA pregnancies. Data from individual studies were pooled using random-effects models and presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Eighteen studies with a total number of over 50 million participants were eligible for inclusion. This current analysis showed that in pregnant women with RA, there was a significantly increased risk of adverse maternal outcomes, including caesarean section (OR, 1.39; 95% CI 1.24-1.55), pre-eclampsia (OR, 1.48; 95% CI 1.19-1.83), gestational hypertension (OR, 1.34; 95% CI 1.07-1.68) and spontaneous abortion (OR, 1.16; 95% CI 1.04-1.29). Similarly, maternal RA during pregnancy was also associated with a significantly increased risk of adverse fetal outcomes, including preterm birth (OR, 1.58; 95% CI 1.44-1.74), small for gestational age (OR, 1.49; 95% CI 1.22-1.82), low birth weight (OR, 1.45; 95% CI 1.30-1.63), congenital anomalies (OR, 1.36; 95% CI 1.01-1.83) and stillborn (OR, 1.38; 95% CI 1.09-1.74). CONCLUSION: Maternal RA is significantly associated with an increased risk of adverse maternal and fetal outcomes. Close monitoring of the clinical status of RA patients before and during pregnancy is essential in clinical practice. Key Points ⢠Pregnant women with rheumatoid arthritis (RA) are at significantly increased risk for adverse maternal and fetal outcomes. ⢠The increased risk of adverse pregnancy outcomes in women with RA may be closely related to medication use and disease activity. ⢠Close monitoring of the clinical status of RA patients before and during pregnancy is essential in clinical practice.
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Artritis Reumatoide , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/epidemiología , Mujeres Embarazadas , Cesárea , Resultado del Embarazo , Artritis Reumatoide/complicacionesRESUMEN
Introduction: It is well-documented that systemic lupus erythematosus (SLE) is associated with dementia. However, the genetic causality of this association remains unclear. Mendelian randomization (MR) was used to investigate the potential causal relationship between SLE and dementia risk in the current study. Methods: We selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from publicly available genome-wide association studies (GWAS). Summary level statistics were obtained from the dementia GWAS database. MR estimates were performed using the inverse variance weighted (IVW) method, MR-Egger method and weighted median (WM) method. Cochran's Q test, the intercept of MR-Egger, MR-Pleiotropy Residual Sum and Outlier method, leave-one-out analysis and funnel plot were applied for sensitivity analyses. Results: No significant causal association was found between SLE and any type of dementia, including Alzheimer's disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. These findings were robust across several sensitivity analyses. Conclusion: Overall, our findings do not support a causal association between SLE and dementia risk.
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Enfermedad de Alzheimer , Lupus Eritematoso Sistémico , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Causalidad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/genética , Enfermedad de Alzheimer/genéticaRESUMEN
Background: Numerous observational studies have revealed that circulating adiponectin (ADPN) is associated with Alzheimer's disease (AD) risk. However, the causality remains unknown. We aimed to assess the causality of circulating ADPN on AD risk using Mendelian randomization (MR). Methods: Fourteen single nucleotide polymorphisms (SNPs) significantly associated with ADPN were selected from publicly available genetic abstract data. We applied these SNPs to two recent large-scale genome-wide association studies (GWAS) of AD, one from the FinnGen consortium and the other from a large meta-analysis. The inverse variance weighted method, MR-Egger method, the weighted median method, the Cochran Q statistic, the MR-Pleiotropy Residual Sum and Outlier methods, and the leave-one-out analysis were applied for MR analyses. Results: In MR analysis, no significant genetic association was found between plasma ADPN levels and AD risk by analyzing the FinnGen consortium GWAS database in the inverse variance weighted method [odds ratio (OR): 0.874, 95% confidence interval (CI): 0.701-1.089, p = 0.230], MR-Egger (OR: 0.944, 95% CI: 0.692-1.288, p = 0.721), and weighted median method (OR: 0.900, 95% CI: 0.678-1.194, p = 0.449). Additionally, the same analysis was conducted for the meta-analysis database, and we found no significant association (OR: 1.000, 95% CI: 0.999-1.001, p = 0.683). Conclusion: Our findings reveal no significant causal association between circulating ADPN and AD risk.
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Background: We aimed to investigate the association of post-thrombolytic D-dimer elevation with symptomatic intracranial hemorrhage (sICH) and functional outcome in AIS patients receiving intravenous thrombolysis. Methods: We retrospectively reviewed our database for patients with AIS who received intravenous thrombolysis between August 2018 and December 2021. ΔD-dimer was calculated as follow-up D-dimer minus baseline D-dimer. Poor functional outcome was defined as 3 months modified Rankin score (mRS) 3-6. sICH was defined as cerebral hemorrhagic transformation in combination with clinical deterioration of National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 24 hours. Binary logistic regression analysis was used to investigate the association of post-thrombolytic D-dimer parameters with sICH and poor functional outcome. The receiver operating characteristic (ROC) curve derived optimal cut-off of different D-dimer parameters was determined at the maximal Youden's Index. Results: A total of 325 patients were finally included. After controlling for clinical variables, follow-up D-dimer level (OR 1.230; 95% CI 1.119 to 1.351; P < 0.001) and ΔD-dimer (OR 1.347; 95% CI 1.165 to 1.559; P < 0.001) were independently associated with poor functional outcome. Additionally, follow-up D-dimer level (OR 1.095; 95% CI 1.009 to 1.188; P = 0.030) was independently related to sICH. The optimal cut-off value of follow-up D-dimer level for predicting sICH was 4185 µg/L (area under the curve 0.760; sensitivity 76.0%; specificity 81.3%); and the optimal cut-off value of follow-up D-dimer level and ΔD-dimer as a predictor for poor functional outcome was projected to be 3838 µg/L and 2190 µg/L, which yielded a sensitivity and a specificity of 62.3%, 84.5% and 73.8%, 85.2%, respectively. Conclusion: Elevated follow-up D-dimer levels are associated with sICH and poor functional outcome in AIS patients following intravenous rt-PA. Moreover, post-thrombolytic D-dimer elevation, measured by ΔD-dimer, was a better predictive biomarker for long-term outcome at 3 months.
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Adaptive optics imaging has enabled the enhanced in vivo retinal visualization of individual cone and rod photoreceptors. Effective analysis of such high-resolution, feature rich images requires automated, robust algorithms. This paper describes RC-UPerNet, a novel deep learning algorithm, for identifying both types of photoreceptors, and was evaluated on images from central and peripheral retina extending out to 30° from the fovea in the nasal and temporal directions. Precision, recall and Dice scores were 0.928, 0.917 and 0.922 respectively for cones, and 0.876, 0.867 and 0.870 for rods. Scores agree well with human graders and are better than previously reported AI-based approaches.
RESUMEN
Mitochondria are the most important organelles and the main reactive oxygen species producers in spermatozoa. The objective of this study was to investigate the effects of mitochondria-targeted antioxidant mitoquinone (MitoQ) supplementation in boar semen extender during cryopreservation on sperm quality, antioxidant status and the changes of sperm mitochondrial proteomic profile. Semen collected from 10 Large White boars was cryopreserved in lactose-egg yolk extender supplemented with various concentrations of MitoQ (0, 5, 10, 20 and 40 µM). After thawing, sperm characteristics, antioxidant status and the abundance of hexose transporters (GLUT 3 and 8) were analyzed. The comprehensive mitochondrial proteomic profiling was performed on spermatozoa in the control and MitoQ10 groups. Supplementation with 10 µM of MitoQ resulted in the highest post-thaw sperm motility and kinematics. Sperm quality, antioxidant capacity and glucose transporter abundance of frozen-thawed boar sperm were also elevated in the MitoQ10 group. Excessive MitoQ (40 µM) supplementation induced a reduction of sperm motility parameters, sperm quality and antioxidant status and the abundance of GLUT3 and 8 proteins. A total of 189 proteins were defied as differentially expressed proteins (DEPs) using fold change (FC) > 1.2 with P < 0.05, and 33 of them were dramatically (FC > 1.5) regulated by MitoQ. These DEPs are mainly involved in sperm motility, energy metabolism and oxidative phosphorylation. Our data suggest that the beneficial effect of MitoQ on cryopreserved boar semen is achieved by regulating sperm antioxidant capacity and the mitochondrial proteins related to motility and metabolism.